Perspectives on Liver Failure: Past and Future

ABSTRACT

Acute liver failure (ALF) remains a potentially devastating syndrome with a high mortality rate. Much interest continues to center upon the possibility of providing effective liver support through various artificial and bioartificial extracorporeal devices. The development of purpose-designed intensive care units for the treatment of ALF allowed a better understanding of the clinical syndrome and its best management, through the ability to conduct detailed clinical observation and clinical trials of new interventions. Survival rates are substantially improved today compared with the mortality rate that approximated 100% when the syndrome was first described nearly five decades ago. Nonetheless, these have plateaued in recent years, prompting one to consider whether major new advances in disease understanding are needed to further improve the overall outcome. A major challenge to a broader understanding of disease pathogenesis and the ability to direct appropriate therapy remains the substantial number of cases of ALF for which no specific etiology can be identified. Much is now known about the basic molecular mechanisms underlying hepatocyte cell death in ALF and an important issue is whether these cell death pathways can, in the future, be interrupted for therapeutic gain. Such considerations would seem most relevant in the early stages of the clinical course, when damage to the liver is not so severe but perhaps programmed to so evolve. A particular challenge will be to reduce hepatocellular death without inhibiting the liver's regenerative potential, given the pleiotropic functions of some of the molecules involved in both processes.

KEYWORDS

Acute liver failure - liver support - cell death

REFERENCES

• 1 Trey C, Davidson C S. The management of fulminant hepatic failure. In: Popper H, Schaffner F Progress in Liver Failure. New York; Grune and Stratton 1970: 282-298
• 2 Bernuau J, Rueff B, Benhamou J P. Fulminant and subfulminant liver failure: definitions and causes.  Semin Liver Dis. 1986;  6 97-106
• 3 O'Grady J G, Schalm S W, Williams R. Acute liver failure: redefining the syndromes.  Lancet. 1993;  342 273-275
• 4 O'Grady J G, Alexander G JM, Hayllar K M et al.. Early indicators of prognosis in fulminant hepatic failure.  Gastroenterology. 1989;  97 439-445
• 5 Kiley J E, Pender J C, Welch H F, Welch C S. Ammonia intoxication treated by haemodialysis.  N Engl J Med. 1958;  259 1156-1161
• 6 Opolon P, Rapin J R, Huguet C et al.. Hepatic failure coma (HFC) treated by polyacrylnitrile membrane (PAN) haemodialysis (HD).  Trans Am Soc Artif Intern Organs. 1976;  22 701-710
• 7 Lee C, Tink A. Exchange transfusion in hepatic coma: report of a case.  Med J Aust. 1958;  45 40-42
• 8 Trey C, Burns D G, Saunders S J. Treatment of hepatic coma by exchange blood transfusion.  N Engl J Med. 1966;  274 473-481
• 9 Larsen F S, Hansen B A, Ejlersen E et al.. Cerebral blood flow, oxygen metabolism and transcranial Doppler sonography during high-volume plasmapheresis in fulminant liver failure.  Eur J Gastroenterol Hepatol. 1996;  8 261-265
• 10 Pascher A, Sauer I M, Neuhaus P. Analysis of allogeneic versus xenogeneic auxiliary organ perfusion in liver failure reveals superior efficacy of human livers.  Int J Artif Organs. 2002;  25 1006-1012
• 11 Burnell J M, Dawborn J K, Epstein R B et al.. Acute hepatic coma treated by cross-circulation or exchange transfusion.  N Engl J Med. 1967;  276 935-943
• 12 Chang T MS. Hemoperfusions over a microencapsulated adsorbent in a patient with hepatic coma.  Lancet. 1972;  2 1371-1372
• 13 Riordan S M, Kurtovic J, Williams R. Fulminant hepatic failure. In: Schiff ER, Sorrell MF, Maddrey WC Schiff's Diseases of the Liver. 10th ed. Philadelphia, PA; Lippincott Williams & Wilkins 2007: 601-636
• 14 Chirito E, Reiter B, Lister C, Chang T MS. Artificial liver: the effect of ACAC microencapsulated charcoal haemoperfusion on fulminant hepatic failure.  Artif Organs. 1977;  1 76-83
• 15 Chang T MS, Lister C, Chirito E, O'Keefe P, Resurreccion E. Effects of haemoperfusion rate and time of initiation of ACAC charcoal haemoperfusion on the survival of fulminant hepatic failure rats.  Trans Am Soc Artif Intern Organs. 1978;  24 243-245
• 16 Tabata Y, Chang T MS. Comparisons of six artificial liver support regimes in fulminant hepatic coma rats.  Trans Am Soc Artif Intern Organs. 1980;  26 394-399
• 17 Niu Z, Shu C D, Jia S R, Li S M. Factors possibly influencing the effects of hemoperfusion in fulminant hepatic failure rats. In: Piskin E, Chang TMS Past, Present and Future of Artificial Organs. Ankara; Meteksan Publishing 1983: 140-151
• 18 Gelfand M C, Winchester J F, Knepshield J H et al.. Biochemical correlates of reversal of hepatic coma coated with charcoal hemoperfusion.  Trans Am Soc Artif Intern Organs. 1978;  24 239-242
• 19 Kennedy H J, Greaves M, Triger D R. Clinical experience with the use of charcoal haemoperfusion: is prostacyclin required?.  Life Support Syst. 1985;  3 115-122
• 20 Tygstrup N, Ranek L. Fulminant hepatic failure.  Clin Gastroenterol. 1981;  10 191-208
• 21 O'Grady J G, Gimson A E, O'Brien C J et al.. Controlled trials of charcoal haemoperfusion and prognostic factors in fulminant hepatic failure.  Gastroenterology. 1988;  94 1186-1192
• 22 Demetriou A A, Brown R S, Busuttil R W et al.. Prospective, randomised, multicenter, controlled trial of a bioartificial liver in treating acute liver failure.  Ann Surg. 2004;  239 660-670
• 23 Ellis A J, Hughes R D, Wendon J A et al.. Pilot-controlled trial of the extracorporeal liver assist device in acute liver failure.  Hepatology. 1996;  24 1446-1451
• 24 Catalina M V, Barrio J, Anaya F et al.. Hepatic and systemic haemodynamic changes after MARS in patients with acute on chronic liver failure.  Liver Int. 2003;  23(suppl 3) 39-43
• 25 Camus C, Lavoue S, Gacouin A et al.. Molecular adsorbent recirculating system dialysis in patients with acute liver failure who are assessed for liver transplantation.  Intensive Care Med. 2006;  32 1817-1825
• 26 Rifai K, Ernst T, Kretschmer U et al.. Prometheus: a new extracorporeal system for the treatment of liver failure.  J Hepatol. 2003;  39 984-990
• 27 Schiodt F V, Atillasoy E, Shakil A O et al.. Etiology and outcome for 295 patients with acute liver failure in the United States.  Liver Transpl Surg. 1999;  5 29-34
• 28 Shakil A O, Kramer D, Mazariegos G V, Fung J J, Rakela J. Acute liver failure: clinical features, outcome analysis and applicability of prognostic criteria.  Liver Transpl. 2000;  6 163-169
• 29 Riordan S M, Williams R. Use and validation of selection criteria for liver transplantation in acute liver failure.  Liver Transpl. 2000;  6 170-173
• 30 Bernal W, Wendon J. Intracranial hypertension in acute liver failure: prevalence and risk factors for development.  Hepatology. 2004;  40(suppl 1) 219A
• 31 Ostapowicz G, Fontana R J, Schiodt F V et al.. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States.  Ann Intern Med. 2002;  137 947-954
• 32 Rolando N, Wade J, Davalos M et al.. The systemic inflammatory response syndrome in acute liver failure.  Hepatology. 2000;  32 734-739
• 33 Tofteng F, Jorgensen L, Hamsen B A et al.. Cerebral microdialyis in patients with fulminant hepatic failure.  Hepatology. 2002;  36 1333-1340
• 34 Shawcross D L, Davies N A, Williams R, Jalan R. Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis.  J Hepatol. 2004;  40 247-254
• 35 Bernal W. Changing patterns of causation and the use of transplantation in the United Kingdom.  Semin Liver Dis. 2003;  23 227-237
• 36 O'Grady J. Acute liver failure. In: O'Grady J, Lake J, Howdle P Comprehensive Clinical Hepatology. London; Mosby 2000: 30.20-30.31
• 37 Bonkovsky H L. Hepatotoxicity associated with supplements containing Chinese green tea (Camellia sinensis).  Ann Intern Med. 2006;  144 68-71
• 38 Molinari M, Watt K D, Kruszyna T et al.. Acute liver failure induced by green tea extracts: case report and review of the literature.  Liver Transpl. 2006;  12 1892-1895
• 39 Jimenez-Saenz M, Martinez-Sanchez C. Green tea extracts and acute liver failure: the need for caution in their use and diagnostic assessment.  Liver Transpl. 2007;  13 1067
• 40 Bernal W, Ma Y, Smith H M, Portmann B, Wendon J, Vergani D. The significance of autoantibodies and immunoglobulins in acute liver failure: a cohort study.  J Hepatol. 2007;  47 664-670
• 41 Riordan S M, Williams R. Mechanisms of hepatocyte injury, multiorgan failure and prognostic criteria in acute liver failure.  Semin Liver Dis. 2003;  23 203-215
• 42 Overturf K, Al-Dhalimy M, Tanguay R et al.. Hepatocytes corrected by gene therapy are selected in vivo in a murine model of hereditary tyrosinaemia type I.  Nat Genet. 1996;  12 266-273
• 43 Overturf K, Al-Dhalimy M, Ou C N, Finegold M, Grompe M. Serial transplantation reveals the stem-cell-like regenerative potential of adult mouse hepatocytes.  Am J Pathol. 1997;  151 1273-1280
• 44 Petersen B E, Bowen W C, Patrene K D et al.. Bone marrow as a potential source of hepatic oval cells.  Science. 1999;  284 1168-1170
• 45 Strom S C, Roy Chowdhury J, Fox I J. Hepatocyte transplantation for the treatment of human disease.  Semin Liver Dis. 1999;  19 39-48